-
Medicine Sep 2022Localized senile pruritus is a continued health problem for the elderly. This study aimed to evaluate the efficacy and safety of artemether emulsion on localized senile... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Localized senile pruritus is a continued health problem for the elderly. This study aimed to evaluate the efficacy and safety of artemether emulsion on localized senile pruritus.
METHODS
Sixty patients diagnosed with senile pruritus were randomized into the artemether emulsion (1%) group or emulsion base group in a 1:1 ratio (the artemether group vs the control group). The patients used artemether emulsion or emulsion base for pruritus twice daily for 2 weeks. The pruritus visual analog scale (VAS) and the rate of adverse events were evaluated in week 0 and week 2.
RESULTS
The VAS scores in week 2 after treatment decreased significantly compared with those before treatment in both groups (P < .05). After treatment, patients receiving the artemether emulsion had significantly lower mean VAS scores compared to those who received the emulsion base (1.21 ± 1.64 vs 3.67 ± 2.97, P < .05). When the VAS scores were compared between the 2 groups before treatment, the effective rate of the artemether group was significantly higher than that of the control group (χ2 = 55, P < .05) in week 2 after treatment. Besides, no adverse events occurred in both groups.
CONCLUSIONS
Both artemether emulsion and emulsion base were effective in treating localized senile pruritus, and artemether emulsion was superior to emulsion base.
Topics: Aged; Artemether; Emulsions; Humans; Pilot Projects; Pruritus; Visual Analog Scale
PubMed: 36107571
DOI: 10.1097/MD.0000000000030472 -
Journal For Immunotherapy of Cancer Sep 2022Water-in-oil emulsion incomplete Freund's adjuvant (IFA) has been used as an adjuvant in preventive and therapeutic vaccines since its development. New generation,... (Review)
Review
Water-in-oil emulsion incomplete Freund's adjuvant (IFA) has been used as an adjuvant in preventive and therapeutic vaccines since its development. New generation, highly purified modulations of the adjuvant, Montanide incomplete seppic adjuvant (ISA)-51 and Montanide ISA-720, were developed to reduce toxicity. Montanide adjuvants are generally considered to be safe, with adverse events largely consisting of antigen and adjuvant dose-dependent injection site reactions (ISRs). Peptide vaccines in Montanide ISA-51 or ISA-720 are capable of inducing both high antibody titers and durable effector T cell responses. However, an efficient T cell response depends on the affinity of the peptide to the presenting major histocompatibility complex class I molecule, CD4 T cell help and/or the level of co-stimulation. In fact, in the therapeutic cancer vaccine setting, presence of a CD4 T cell epitope seems crucial to elicit a robust and durable systemic T cell response. Additional inclusion of a Toll-like receptor ligand can further increase the magnitude and durability of the response. Use of extended peptides that need a processing step only accomplished effectively by dendritic cells (DCs) can help to avoid antigen presentation by nucleated cells other than DC. Based on recent clinical trial results, therapeutic peptide-based cancer vaccines using emulsions in adjuvant Montanide ISA-51 can elicit robust antitumor immune responses, provided that sufficient tumor-specific CD4 T cell help is given in addition to CD8 T cell epitopes. Co-treatment with PD-1 T cell checkpoint inhibitor, chemotherapy or other immunomodulatory drugs may address local and systemic immunosuppressive mechanisms, and further enhance efficacy of therapeutic cancer peptide vaccines in IFA and its modern variants. Blinded randomized placebo-controlled trials are critical to definitively prove clinical efficacy. Mineral oil-based adjuvants for preventive vaccines, to tackle spread and severity of infectious disease, induce immune responses, but require more studies to reduce toxicity.
Topics: Humans; Adjuvants, Immunologic; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Emulsions; Immunotherapy; Neoplasms; Peptides; Vaccines, Subunit
PubMed: 36939214
DOI: 10.1136/jitc-2022-004709 -
Journal of Controlled Release :... Sep 2022Two widely applied enabling drug delivery approaches, self-nanoemulsifying drug delivery systems (SNEDDS) and amorphous solid dispersions (ASD), were combined, with the...
Two widely applied enabling drug delivery approaches, self-nanoemulsifying drug delivery systems (SNEDDS) and amorphous solid dispersions (ASD), were combined, with the aim of enhancing physical stability, solubilization and absorption of the model drug ritonavir. Ritonavir was loaded at a concentration above its saturation solubility (S) in the SNEDDS (superSNEDDS, 250% of S). An ASD of ritonavir with polyvinylpyrrolidone-vinyl acetate copolymers (Kollidon® VA64) was prepared by ball milling. Relevant control formulations, which include conventional SNEDDS (90% of S), superSNEDDS with a physical mix of Kollidon® VA64 and ritonavir (superSNEDDS+PM) and an aqueous suspension of ritonavir were used. A pharmacokinetic (PK) study in rats was performed to assess the relative bioavailability of ritonavir after oral administration. This was followed by evaluating the formulations in a novel two-step in vitro lipolysis model simulating rat gastric and intestinal conditions. The addition of a ritonavir containing ASD to superSNEDDS increased the degree of supersaturation from 250% to 275% S in the superSNEDDS and the physical stability (absence of drug recrystallization) of the system from 48 h to 1 month under ambient conditions. The PK study in rats displayed significantly higher C and AUC (3-fold increase) and faster T for superSNEDDS+ASD compared to the conventional SNEDDS whilst containing 3 times less lipid than the latter. Furthermore, superSNEDDS+ASD were able to keep the drug solubilised during in vitro lipolysis to the same degree as the conventional SNEDDS. These findings suggest that dissolving an ASD in a superSNEDDS can contribute to the development of novel oral delivery systems with increased bioavailability for poorly water-soluble drugs.
Topics: Administration, Oral; Animals; Biological Availability; Drug Delivery Systems; Emulsions; Lipids; Nanoparticles; Particle Size; Povidone; Rats; Ritonavir; Solubility; Water
PubMed: 35787914
DOI: 10.1016/j.jconrel.2022.06.057 -
Molecules (Basel, Switzerland) Oct 2023Cannabidiol (CBD) is a promising natural agent for treating psoriasis. CBD activity is attributed to inhibition of NF-kB, IL-1β, IL-6, and IL-17A. The present study...
Cannabidiol (CBD) is a promising natural agent for treating psoriasis. CBD activity is attributed to inhibition of NF-kB, IL-1β, IL-6, and IL-17A. The present study evaluated the anti-psoriatic effect of cannabidiol in lipid-stabilized nanoparticles (LSNs) using an imiquimod (IMQ)-induced psoriasis model in mice. CBD-loaded LSNs were stabilized with three types of lipids, Cetyl alcohol (CA), Lauric acid (LA), and stearic-lauric acids (SALA), and were examined in-vitro using rat skin and in-vivo using the IMQ-model. LSNs loaded with coumarin-6 showed a localized penetration depth of about 100 µm into rat skin. The LSNs were assessed by the IMQ model accompanied by visual (psoriasis area severity index; PASI), histological, and pro-psoriatic IL-17A evaluations. Groups treated with CBD-loaded LSNs were compared to groups treated with CBD-containing emulsion, unloaded LSNs, and clobetasol propionate, and to an untreated group. CBD-loaded LSNs significantly reduced PASI scoring compared to the CBD emulsion, the unloaded LSNs, and the untreated group (negative controls). In addition, SALA- and CA-containing nanoparticles significantly inhibited IL-17A release, showing a differential response: SALA > CA > LA. The data confirms the effectiveness of CBD in psoriasis therapy and underscores LSNs as a promising platform for delivering CBD to the skin.
Topics: Mice; Rats; Animals; Interleukin-17; Cannabidiol; Emulsions; Psoriasis; Skin; Imiquimod; Nanoparticles; Lipids; Disease Models, Animal; Mice, Inbred BALB C
PubMed: 37836750
DOI: 10.3390/molecules28196907 -
Journal of Controlled Release :... Aug 2022To date, buccal administration of lipophilic drugs is still a major challenge due to their poor solubility in saliva and limited penetration into mucosal tissues. To...
To date, buccal administration of lipophilic drugs is still a major challenge due to their poor solubility in saliva and limited penetration into mucosal tissues. To overcome these limitations, we developed electrospun patches combining the benefits of mucoadhesive fibers and self-emulsifying drug delivery systems (SEDDS). The fiber system comprises a combination of mucoadhesive thiolated polyacrylic acid fibers and SEDDS-loaded fibers fabricated by parallel electrospinning. The resulting mucoadhesive electrospun SEDDS patches were systemically investigated for fiber characteristics, self-emulsification, mucoadhesion, drug penetration into porcine buccal tissue and biocompatibility. The patches showed high encapsulation efficiency for SEDDS without causing fiber defects or leakage. SEDDS incorporation enhanced the spinning process and reduced the fiber diameter and fiber size distribution. Hydration-dependent self-emulsification provided a controlled release of curcumin being encapsulated in nano-scaled o/w emulsion for over 3 h. Due to the thiolated polyacrylic acid fibers, the buccal residence time of patches was 200-fold prolonged. Further, they promoted a significantly increased drug penetration into buccal tissue compared to fiber patches without SEDDS. Finally, biocompatibility and improved therapeutic effects of curcumin-loaded patches on human keratinocytes and fibroblasts were confirmed. Mucoadhesive electrospun SEDDS patches represent a promising approach to overcome current challenges in the oromucosal delivery of lipophilic drugs to unlock their full therapeutic potential.
Topics: Administration, Buccal; Animals; Curcumin; Drug Delivery Systems; Emulsions; Humans; Solubility; Swine
PubMed: 35718212
DOI: 10.1016/j.jconrel.2022.06.023 -
International Journal of Nanomedicine 2024Therapeutic proteins and peptides offer great advantages compared to traditional synthetic molecular drugs. However, stable protein loading and precise control of...
BACKGROUND
Therapeutic proteins and peptides offer great advantages compared to traditional synthetic molecular drugs. However, stable protein loading and precise control of protein release pose significant challenges due to the extensive range of physicochemical properties inherent to proteins. The development of a comprehensive protein delivery strategy becomes imperative accounting for the diverse nature of therapeutic proteins.
METHODS
Biodynamers are amphiphilic proteoid dynamic polymers consisting of amino acid derivatives connected through pH-responsive dynamic covalent chemistry. Taking advantage of the amphiphilic nature of the biodynamers, PNCs and DEs were possible to be prepared and investigated to compare the delivery efficiency in drug loading, stability, and cell uptake.
RESULTS
As a result, the optimized PNCs showed 3-fold encapsulation (<90%) and 5-fold loading capacity (30%) compared to DE-NPs. PNCs enhanced the delivery efficiency into the cells but aggregated easily on the cell membrane due to the limited stability. Although DE-NPs were limited in loading capacity compared to PNCs, they exhibit superior adaptability in stability and capacity for delivering a wider range of proteins compared to PNCs.
CONCLUSION
Our study highlights the potential of formulating both PNCs and DE-NPs using the same biodynamers, providing a comparative view on protein delivery efficacy using formulation methods.
Topics: Peptides; Emulsions; Humans; Proteins; Drug Delivery Systems; Polymers; Nanoparticles; Hydrogen-Ion Concentration; Amino Acids; Drug Carriers; Drug Liberation; Cell Survival
PubMed: 38784761
DOI: 10.2147/IJN.S448578 -
Journal of Colloid and Interface Science May 2020Cytotoxic drugs tend to have substantial side effects on healthy tissues leading to systemic toxicity, limited tolerated doses and reduced drug efficacy. A prominent...
Cytotoxic drugs tend to have substantial side effects on healthy tissues leading to systemic toxicity, limited tolerated doses and reduced drug efficacy. A prominent research area focuses on encapsulating cytotoxic drugs for targeted delivery to cancer tissues. However, existing carriers suffer from low drug loading levels and high drug leaching both when circulating systemically and when accumulating in non-target organs. These challenges mean that only few encapsulation technologies for delivery of cytotoxic drugs have been adopted for clinical use. Recently, we have demonstrated efficient manufacture of impermeable metal-shell/liquid core microcapsules that permit localised delivery by triggering release with ultrasound. This method has the potential to improve on existing methods for localised drug delivery because it:We demonstrate here the further miniaturization of both the emulsion droplet template and the thickness of the surrounding metal shell to the nanoscale in an attempt to take advantage of the EPR effect and the excretion of nanoparticles by the hepatobiliary system.
Topics: Antineoplastic Agents, Phytogenic; Drug Carriers; Drug Delivery Systems; Emulsions; Humans; Metal Nanoparticles; Paclitaxel; Particle Size; Platinum; Surface Properties
PubMed: 32045739
DOI: 10.1016/j.jcis.2019.12.018 -
F1000Research 2023The nonsteroidal anti-inflammatory medication meloxicam (MLX) belongs to the oxicam family and is used to reduce inflammation and pain. The aim of this study was to...
The nonsteroidal anti-inflammatory medication meloxicam (MLX) belongs to the oxicam family and is used to reduce inflammation and pain. The aim of this study was to improve MLX's dispersibility and stability by producing it as a liquid self-microemulsifying drug delivery system since it is practically insoluble in water. Five different formulations were made by adjusting the amounts of propylene glycol, Transcutol P, Tween 80, and oleic acid oil and establishing a pseudo-ternary diagram in ratios of 1:1, 1:2, 1:3, 1:4, and 3:4, respectively. All of the prepared formulations were tested for a variety of properties, including thermodynamic stability, polydispersity index, particle size distributions, dilution resistance, drug contents, dispersibility, solubility of the drug, and emulsification time. F5 was chosen as the optimal MLX liquid self-microemulsion due to its higher drug content (99.8%), greater release (100% at 40 min), smaller droplet size (63 nm), lower polydispersity index (PDI) value (0.3), and higher stability (a zeta potential of -81 mV). According to the data provided here, the self-microemulsifying drug delivery system is the most practical method for improving the dispersibility and stability of MLX.
Topics: Meloxicam; Surface-Active Agents; Emulsions; Drug Delivery Systems; Polysorbates
PubMed: 37359788
DOI: 10.12688/f1000research.130749.2 -
Scientific Reports Apr 2023Simvastatin (SV) is a poorly soluble drug; its oral administration is associated with a significant problem: Myopathy. The present study aims to formulate SV...
Simvastatin (SV) is a poorly soluble drug; its oral administration is associated with a significant problem: Myopathy. The present study aims to formulate SV microsponges that have the potential to minimize the myotoxicity accompanying the oral administration of the drug. SV microsponges were prepared by exploiting the emulsion solvent evaporation technique. The % entrapment efficiency (%EE) of the drug approached 82.54 ± 1.27%, the mean particle size of SV microsponges ranged from 53.80 ± 6.35 to 86.03 ± 4.79 µm in diameter, and the % cumulative drug release (%CDR) of SV from microsponges was significantly higher than that from free drug dispersion much more, the specific surface area of the optimized microsponges formulation was found to be 16.6 m/g revealed the porosity of prepared microsponges. Histological and glycogen histochemical studies in the skeletal muscles of male albino rats revealed that microsponges were safer than free SV in minimizing myotoxicity. These findings were proven by Gene expression of Mitochondrial fusion and fission (Mfn1) & (Fis1) and (Peroxisome proliferator-activated receptor gamma co-activator 1α) PGC-1α. Finally, our study ascertained that SV microsponges significantly decreased the myotoxicity of SV.
Topics: Male; Drug Delivery Systems; Drug Liberation; Emulsions; Myotoxicity; Porosity; Simvastatin; Animals; Rats
PubMed: 37031209
DOI: 10.1038/s41598-023-32545-0 -
Journal of Nanobiotechnology Jul 2021Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based...
BACKGROUND
Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential.
RESULTS
Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation.
CONCLUSIONS
The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy.
Topics: Albumins; Animals; Antineoplastic Agents; Cell Line, Tumor; Disease Models, Animal; Drug Carriers; Emulsions; Female; Immunosuppressive Agents; Immunotherapy; Liposomes; Mice; Mice, Inbred BALB C; Mice, Nude; Nanomedicine; Nanoparticles; Paclitaxel; Triple Negative Breast Neoplasms
PubMed: 34225762
DOI: 10.1186/s12951-021-00946-w